Methylmercury affects the expression of hypothalamic neuropeptides that control body weight in C57BL/6J mice

Beatriz Ferrer, Tanara Vieira Peres, Alessandra Antunes dos Santos, Julia Bornhorst, Patricia Morcillo, Cinara Ludvig Gonçalves, Michael Aschner

Research output: Contribution to journalArticle

Abstract

Methylmercury (MeHg) is an environmental pollutant that affects primarily the central nervous system (CNS), causing neurological alterations. An early symptom of MeHg poisoning is the loss of body weight and appetite. Moreover, the CNS has an important role in controlling energy homeostasis. It is known that in the hypothalamus nutrient and hormonal signals converge to orchestrate control of body weight and food intake. In this study, we investigated if MeHg is able to induce changes in the expression of key hypothalamic neuropeptides that regulate energy homeostasis. Thus, hypothalamic neuronal mouse cell line GT 1-7 was treated with MeHg at different concentrations (0, 0.5, 1, and 5 mM). MeHg induced the expression of the anorexigenic neuropeptide pro-omiomelanocortin (Pomc) and the orexigenic peptide Agoutirelated peptide (Agrp) in a concentration-dependent manner, suggesting deregulation of mechanisms that control body weight. To confirm these in vitro observations, 8-week-old C57BL/6J mice (males and females) were exposed to MeHg in drinking water, modeling the most prevalent exposure route to this metal. After 30-day exposure, no changes in body weight were detected. However, MeHg treated males showed a significant decrease in fat depots. Moreover, MeHg affected the expression of hypothalamic neuropeptides that control food intake and body weight in a gender- and dose-dependent manner. Thus, MeHg increases Pomc mRNA only in males in a dose-dependent way, and it does not have effects on the expression of Agrp mRNA. The present study shows, for first time, that MeHg is able to induce changes in hypothalamic neuropeptides that regulate energy homeostasis, favoring an anorexigenic/catabolic profile.

Original languageEnglish (US)
Pages (from-to)557-568
Number of pages12
JournalToxicological Sciences
Volume163
Issue number2
DOIs
StatePublished - Jun 1 2018

Fingerprint

Neuropeptides
Inbred C57BL Mouse
Body Weight
Homeostasis
Neurology
Peptides
Central Nervous System
Eating
Environmental Pollutants
Messenger RNA
Body Weight Changes
Deregulation
Appetite
Drinking Water
Poisoning
Nutrients
Hypothalamus
Metals
Fats
Cells

Keywords

  • Control body weight
  • Glucose homeostasis
  • Hypothalamus
  • Methylmercury
  • Neuropeptides

ASJC Scopus subject areas

  • Toxicology

Cite this

Methylmercury affects the expression of hypothalamic neuropeptides that control body weight in C57BL/6J mice. / Ferrer, Beatriz; Peres, Tanara Vieira; Santos, Alessandra Antunes dos; Bornhorst, Julia; Morcillo, Patricia; Gonçalves, Cinara Ludvig; Aschner, Michael.

In: Toxicological Sciences, Vol. 163, No. 2, 01.06.2018, p. 557-568.

Research output: Contribution to journalArticle

Ferrer, Beatriz ; Peres, Tanara Vieira ; Santos, Alessandra Antunes dos ; Bornhorst, Julia ; Morcillo, Patricia ; Gonçalves, Cinara Ludvig ; Aschner, Michael. / Methylmercury affects the expression of hypothalamic neuropeptides that control body weight in C57BL/6J mice. In: Toxicological Sciences. 2018 ; Vol. 163, No. 2. pp. 557-568.
@article{d61b97b71131476a8e5ce18a7cd78d6b,
title = "Methylmercury affects the expression of hypothalamic neuropeptides that control body weight in C57BL/6J mice",
abstract = "Methylmercury (MeHg) is an environmental pollutant that affects primarily the central nervous system (CNS), causing neurological alterations. An early symptom of MeHg poisoning is the loss of body weight and appetite. Moreover, the CNS has an important role in controlling energy homeostasis. It is known that in the hypothalamus nutrient and hormonal signals converge to orchestrate control of body weight and food intake. In this study, we investigated if MeHg is able to induce changes in the expression of key hypothalamic neuropeptides that regulate energy homeostasis. Thus, hypothalamic neuronal mouse cell line GT 1-7 was treated with MeHg at different concentrations (0, 0.5, 1, and 5 mM). MeHg induced the expression of the anorexigenic neuropeptide pro-omiomelanocortin (Pomc) and the orexigenic peptide Agoutirelated peptide (Agrp) in a concentration-dependent manner, suggesting deregulation of mechanisms that control body weight. To confirm these in vitro observations, 8-week-old C57BL/6J mice (males and females) were exposed to MeHg in drinking water, modeling the most prevalent exposure route to this metal. After 30-day exposure, no changes in body weight were detected. However, MeHg treated males showed a significant decrease in fat depots. Moreover, MeHg affected the expression of hypothalamic neuropeptides that control food intake and body weight in a gender- and dose-dependent manner. Thus, MeHg increases Pomc mRNA only in males in a dose-dependent way, and it does not have effects on the expression of Agrp mRNA. The present study shows, for first time, that MeHg is able to induce changes in hypothalamic neuropeptides that regulate energy homeostasis, favoring an anorexigenic/catabolic profile.",
keywords = "Control body weight, Glucose homeostasis, Hypothalamus, Methylmercury, Neuropeptides",
author = "Beatriz Ferrer and Peres, {Tanara Vieira} and Santos, {Alessandra Antunes dos} and Julia Bornhorst and Patricia Morcillo and Gon{\cc}alves, {Cinara Ludvig} and Michael Aschner",
year = "2018",
month = "6",
day = "1",
doi = "10.1093/toxsci/kfy052",
language = "English (US)",
volume = "163",
pages = "557--568",
journal = "Toxicological Sciences",
issn = "1096-6080",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Methylmercury affects the expression of hypothalamic neuropeptides that control body weight in C57BL/6J mice

AU - Ferrer, Beatriz

AU - Peres, Tanara Vieira

AU - Santos, Alessandra Antunes dos

AU - Bornhorst, Julia

AU - Morcillo, Patricia

AU - Gonçalves, Cinara Ludvig

AU - Aschner, Michael

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Methylmercury (MeHg) is an environmental pollutant that affects primarily the central nervous system (CNS), causing neurological alterations. An early symptom of MeHg poisoning is the loss of body weight and appetite. Moreover, the CNS has an important role in controlling energy homeostasis. It is known that in the hypothalamus nutrient and hormonal signals converge to orchestrate control of body weight and food intake. In this study, we investigated if MeHg is able to induce changes in the expression of key hypothalamic neuropeptides that regulate energy homeostasis. Thus, hypothalamic neuronal mouse cell line GT 1-7 was treated with MeHg at different concentrations (0, 0.5, 1, and 5 mM). MeHg induced the expression of the anorexigenic neuropeptide pro-omiomelanocortin (Pomc) and the orexigenic peptide Agoutirelated peptide (Agrp) in a concentration-dependent manner, suggesting deregulation of mechanisms that control body weight. To confirm these in vitro observations, 8-week-old C57BL/6J mice (males and females) were exposed to MeHg in drinking water, modeling the most prevalent exposure route to this metal. After 30-day exposure, no changes in body weight were detected. However, MeHg treated males showed a significant decrease in fat depots. Moreover, MeHg affected the expression of hypothalamic neuropeptides that control food intake and body weight in a gender- and dose-dependent manner. Thus, MeHg increases Pomc mRNA only in males in a dose-dependent way, and it does not have effects on the expression of Agrp mRNA. The present study shows, for first time, that MeHg is able to induce changes in hypothalamic neuropeptides that regulate energy homeostasis, favoring an anorexigenic/catabolic profile.

AB - Methylmercury (MeHg) is an environmental pollutant that affects primarily the central nervous system (CNS), causing neurological alterations. An early symptom of MeHg poisoning is the loss of body weight and appetite. Moreover, the CNS has an important role in controlling energy homeostasis. It is known that in the hypothalamus nutrient and hormonal signals converge to orchestrate control of body weight and food intake. In this study, we investigated if MeHg is able to induce changes in the expression of key hypothalamic neuropeptides that regulate energy homeostasis. Thus, hypothalamic neuronal mouse cell line GT 1-7 was treated with MeHg at different concentrations (0, 0.5, 1, and 5 mM). MeHg induced the expression of the anorexigenic neuropeptide pro-omiomelanocortin (Pomc) and the orexigenic peptide Agoutirelated peptide (Agrp) in a concentration-dependent manner, suggesting deregulation of mechanisms that control body weight. To confirm these in vitro observations, 8-week-old C57BL/6J mice (males and females) were exposed to MeHg in drinking water, modeling the most prevalent exposure route to this metal. After 30-day exposure, no changes in body weight were detected. However, MeHg treated males showed a significant decrease in fat depots. Moreover, MeHg affected the expression of hypothalamic neuropeptides that control food intake and body weight in a gender- and dose-dependent manner. Thus, MeHg increases Pomc mRNA only in males in a dose-dependent way, and it does not have effects on the expression of Agrp mRNA. The present study shows, for first time, that MeHg is able to induce changes in hypothalamic neuropeptides that regulate energy homeostasis, favoring an anorexigenic/catabolic profile.

KW - Control body weight

KW - Glucose homeostasis

KW - Hypothalamus

KW - Methylmercury

KW - Neuropeptides

UR - http://www.scopus.com/inward/record.url?scp=85048086140&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048086140&partnerID=8YFLogxK

U2 - 10.1093/toxsci/kfy052

DO - 10.1093/toxsci/kfy052

M3 - Article

VL - 163

SP - 557

EP - 568

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -